The limited therapeutic benefit from nitroimidazoles has renewed the interest in normobaric oxygen as a hypoxic cell radiosensitizer. In this experimental study we have tried to modify the oxygenation of a C3H mammary carcinoma by flushing tumor-bearing mice with oxygen or carbogen for 5 min before and during treatment. The response to these treatments was evaluated by the changes in radiation-induced tumor control (TCD50) and by the changes in tumor hypoxic fraction (HF). Irradiation was given either as a large, single dose or as five equal, daily fractions. High levels of oxygen in the inspired air were found to decrease the TCD50 significantly. The enhancement ratios were in the range of 1.2-1.4 (p less than 0.05) for both single dose and fractionated irradiation, which suggests that hypoxic cells may be important even when reoxygenation is believed to be complete between fractions. The change in TCD50 corresponded to a decrease in the fraction of clonogenic hypoxic cells from 12% to 3-4% (p less than 0.05). Tumor blood flow was not significantly influenced by the gas treatment. This study thus shows that normobaric oxygen/carbogen inhalation may significantly improve the local tumor control by reducing the diffusion related hypoxia within tumors.